CANCER CELL BIOLOGY AND SIGNALING PROGRAM (CCBS) ABSTRACT: The purpose of CCBS, a Discipline-Based Program, is to make fundamental mechanistic discoveries into signaling pathways that are dysregulated in human cancer and to translate findings into new treatment opportunities. Common themes are to: 1) Integrate genomic, biochemical and functional analyses to determine the role and dysregulation of signaling pathways in relevant cancer models; 2) Identify mechanisms of resistance to targeted inhibitors; and 3) Characterize the role of the stroma in the tumor microenvironment. Current specific aims are: Aim 1: Discover mechanisms regulating cell growth & metastasis by heterotrimeric and monomeric GTPases Aim 2: Characterize the role of the tumor microenvironment in regulating protein kinase signaling pathways and metabolism Aim 3: Identify the regulation and role of inflammation and cytokine signaling The CCBS Program has 42 members that include basic scientists, clinical researchers, and population scientists that have made high-impact discoveries at the bench and in the clinic. Members generated 776 publications, an increase of +19.4% over the prior project period. Of these, 135(17.4%) were intra- programmatic, an increase of +58.2%; 164 were inter-programmatic (21.1%). Overall impact has improved with 7.5% appearing in journals with an impact factor >10 and an average impact factor of 5.6. In 2016, SKCC also began to track collaborations with authors from other NCI-designated Cancer Centers; at present, 34.2% of CCBS Program publications were in collaboration with authors from other NCI-designated Centers. The overall impact of CCBS is illustrated by the number of high-impact fundamental discoveries that have been published in the last funding cycle, including in Cell, PNAS, JAMA, J. Clin Invest., J. Clin Oncol., Nature and Nature Comm. In the last funding period, CCBS members were productive in securing funding. Notably, the mechanism for calculating total and direct costs has changed since the last CCSG review, now requiring exclusion of funding sources that were allowable in the last review. Furthermore, SKCC was last reviewed during the peak of ARRA funding. Despite these barriers in comparing current funding totals versus the last review, CCBS remains strong. Total cancer relevant funding increased from $13.7M to $17.1M total costs (+29.0 %) with direct costs also increasing from $9.4M to $12.2 (+29.8%). Annual peer-reviewed funding is steady from the last review at $11.7M total/ $7.7M direct, with 27.2 % of peer-reviewed funding derived from NCI, and 32.8% from combined federal cancer-dedicated peer review sources (NCI + Department of Defense Cancer Programs).